咳嗽变异型哮喘与HLA-DQA1 DQB1基因多态性研究

Association Research between Human Leukocyte Antigen (HLA) Class Ⅱ DQA1 and DQB1 Gene Polymorphisms and Cough Variant Asthma

目的:研究人类白细胞抗原(HLA)Ⅱ-DQA1、DQB1基因多态性与咳嗽变异型哮喘的相关性。方法:采用序列特异性引物聚合酶链反应的方法,对HLAⅡ-DQA1、DQB1进行基因分型,对无血缘关系的30例咳嗽变异型哮喘患者、32例典型支气管哮喘患者和33例健康人进行了HLAII-DQA1、DQB1基因型检测。结果:①3组间,典型支气管哮喘患者组HLA-DQA1*0201*0301*0501基因频率明显高于咳嗽变异型哮喘患者组与健康对照组(P<0.05),而咳嗽变异型哮喘患者组与健康对照组之间无统计学意义(P>0.05);咳嗽变异型哮喘患者组与典型支气管哮喘患者组HLA-DQA1*0302基因频率明显高于健康对照组(P<0.05),但咳嗽变异型哮喘患者组与典型支气管哮喘患者组比较,咳嗽变异型哮喘患者组HLA-DQA1*0302基因频率明显低于典型支气管哮喘患者组(P<0.05)。②咳嗽变异型哮喘患者组与典型支气管哮喘患者组HLA-DQB1*0301基因频率明显低于健康对照组(P<0.05),咳嗽变异型哮喘患者组与典型支气管哮喘患者组之间无统计学意义(P>0.05)。结论:本研究结果显示,咳嗽变异型哮喘与典型支气管哮喘一样,属多基因遗传疾病,在HLA-DQA1、DQB1等位基因表达上有共性,二者存在着部分相同的免疫遗传机制;但本研究结果同时显示,咳嗽变异型哮喘在HLA-DQA1等位基因的表达上与典型支气管哮喘又有所区别,其基因频率表达介于正常健康人与典型支气管哮喘患者之间,这为咳嗽变异型性哮喘与典型支气管哮喘在临床表现及治疗上的异同提供了免疫遗传依据,同时将为今后通过转基因彻底根治咳嗽变异型哮喘提供免疫遗传学依据。

Objective：To investigate the association between human leukocyte antigen（HLA）class Ⅱ DQA1 and DQB1 gene polymorphisms and cough variant asthma.Methods： Sequence-specific primen-polyerase chainreaction（PCR-SSP）was used to identify HLA-DQA1 and HLA-DQB1 genotypes in 30 cases with cough variant asthma,who were diagnosed with bronchial reactivity to methacholine（Mch） and bronchial reversibility,32 cases with typical bronchial asthma and 33 cases of healthy volunteers as control.Results：Among the three groups,the allele frequencies of DQA1＊0201＊0301＊0501 were significantly higher in patients with typical bronchial asthma than that in patients with cough variant asthma and helthy controls（P0.05）,There was no statistical difference between the patients with cough variant asthma and healthy controls（P0.05）.HLA-DQA1＊0302 allele was significantly higher in the patients with cough variant asthma and inpatients with typical bronchial asthma than that in healthy controls（P0.05）,while the allele frequency of HLA-DQA1＊0302 was significantly decreased in patients with cough variant asthma than that in patients with typical bronchial asthma（P0.05）.The frequency of HLA-DQB1＊0301 allele was significantly lower in patients with cough variant asthma and typical bronchial asthma than that in healthy controls（P0.05）.Conclusions： The results revealed that cough variant asthma is apolygenetic disease as well as typical asthma,which in HLA-DQA1 and DQB1 alleles are commonly expressed.They might have some similar immungenetic mechanism.Moreover,the expression of HLA-DQAL in patients with cough variant asthma is different from those with typical asthma adn its gene frequency is higher than healthypatients,but lower than patients with typical asthma.This study provides a new immungenetic mechanism of understanding clinical symptoms and treatment of cough variant asthma and typical asthma.Meanwhile,this study may provide immungenetic basis to cure cough variant asthma by transgene therapy in future.